Medicines and other agents have been administered with needles and syringes for many years. Needles and syringes have posed a variety of problems for patients and medical personnel who administer agents to the patients, including injection safety, needle stick injury, disposal problems, transmission of blood borne diseases, and needle shortages during mass vaccination campaigns. The replacement of needles and syringes as the primary delivery vehicle for agents has the potential for tremendous cost savings, increased safety and reduction of biomedical wastes.
Currently there exist at least three methods for administration of agents using pulmonary delivery devices, including; nebulizers, metered dose inhalers, and dry powder inhalers. Much of the equipment used for aerosol delivery is cumbersome and has not been widely employed for many treatment methods. Nebulizers are commonly used in hospitals for the treatment of respiratory diseases. In practice, a nebulizer uses compressed gases to convert a solution of the agent into fine droplets. The droplets are administered to the patient through an air stream that the patient breathes inwardly through a mouthpiece or mask. As the patient breathes, the agent is delivered to the patient's lungs and absorbed therein.
Typically, nebulizers rely upon an external compressed gas source to convert a solution of the agent into fine droplets. As a result of the need for an external source of compressed gas, nebulizers tend to be bulky and difficult to move. Further, the effectiveness of a nebulizer depends upon proper inhalation by the patient, which can be difficult to monitor and to teach to the patient.
Additionally, nebulizers fall short of an adequate design because they fail to provide a consistent, uniform droplet size. Instead, nebulizers produce a wide range of droplet sizes, often with the droplet size being too large for lung absorption. Thus, the patient either gets less of the agent than is necessary or the nebulizer must administer more of the agent than is necessary so that at least an effective amount will be delivered to the patient. With such methods, the agent is wasted and there is a risk that the patient will inhale too much of the agent and be overdosed.
Currently used jet nebulizers function in the same general way. Liquid is drawn up to an air nozzle by capillary forces and/or the Bernoulli effect. At the nozzle, a high-speed air jet shatters the liquid into droplets. Droplets blast against an impactor to break them up further into smaller droplets. Like most atomization processes, this droplet generation process results in a size distribution. To obtain the desired small aerosol droplets, baffles capture large droplets (which cannot follow the airflow path well), leaving the fine aerosol in the output stream of the nebulizer. The larger droplets recycle to the liquid reservoir of the nebulizer.
This nebulization process is inherently inefficient. Measurements show that typical nebulizers only convert about 1% of the aspirated liquid to fine aerosol droplets. Thus, liquid will normally be recycled well in excess of twenty times before it reaches the desired size and is exhausted from the nebulizer. The inefficiency of the jet nebulizer poses problems to its use for aerosol vaccination. High velocity is needed in the air jet to provide the energy required to break the liquid into sufficiently small droplets, necessitating relatively high air supply pressures in flow rates. Compressing air to provide this supply requires significant power, either human or electric.
Fluid recycling in the nebulizer in the small amount of vaccine required for each dose results in the inability to operate on a dose-by-dose basis. Many doses need to be present in the nebulizer in order for droplet coalescence on the baffles in other surfaces to return liquid to the reservoir. In addition, the repeated mechanical stress of atomization on the vaccination particles in the liquid risks diminishing the viability of the vaccine.
Further compounding the inherent problems found in prior nebulizer design is the required duration of drug administration. Typically, nebulizers require several minutes of use to administer a proper drug dosage. Accordingly, the patient is required to maintain the desired breathing technique throughout the application period. Even so, such precision by the patient is seldom found in practice. Therefore, such nebulizers are inefficient and impractical drug delivery devices.
Another system for delivering an agent is a metered dose inhaler (MDI). MDI represents the most widely used system for pulmonary delivery of agents, especially pharmaceuticals, and consists in part of a canister which holds the agent, together with a propellant, typically a chlorofluorocarbon (CFC). A patient may self-administer the agent by activating the canister, thereby releasing a high velocity air stream consisting of a mixture of air and the agent. As with the nebulizers, MDI's produce a wide range of droplet sizes; however, only a small portion of the droplets produced are absorbed by the patient.
Administration of the agent is effective only if the patient coordinates inhalation with activation of the canister. Problems arise if the patient fails to coordinate inhalation with the release of the agent by the canister. Specifically, the agent can be deposited at the back of the throat, rather than on the interior walls of the lungs, thereby causing the agent to be ingested, digested and expelled from the patient rather than being absorbed directly by the bloodstream or being effective on site in the lungs. Although spacer devices have been developed to overcome the difficulty of press-and-breathe coordination, problems still exist with the inhalation technique and compliance monitoring. Accordingly, MDI's have not proved to be an effective system of pulmonary delivery.
Additionally, MDIs suffer from the reliance on a propellant. Chlorofluorocarbons have long been the propellant of choice, and these compounds have severe environmental consequences. Thus, the use of chlorofluorocarbons are being phased out. The replacement propellants may not be as safe or effective for pulmonary delivery devices.
Still another method of pulmonary or inhalant delivery is the dry powder inhaler (DPI), introduced to the marketplace as a replacement for the MDI systems, particularly to overcome the need for a chlorofluorocarbon propellants. A DPI uses a portable canister that stores an agent in a dry powder state. Patients can self-administer the agent by inhaling small, dry particles. Unlike other methods of pulmonary delivery, agents used with DPI's must be prepared as a solid, must be able to tolerate storage in a solid phase, and must be capable of complete dispersion at the point of delivery. As a result, many agents are not compatible for use with the DPI method of delivery. Accordingly, DPI's may be an ineffective method of delivery of agents.
Thus, a need exists for effective systems and methods for administering an agent in an aerosol form, without a needle, and in more accurate dosages. Further, a need exists for portable delivery systems that provide an agent to patients in a form that may be rapidly absorbed.